8-羟基喹啉-2(1H)-酮类似物作为潜在的β-激动剂：设计、合成与活性研究。
8-Hydroxyquinolin-2(1H)-one analogues as potential β-agonists: Design, synthesis and activity study.
机构信息
Department of Medicinal Chemistry, School of Pharmaceutical Engineering, Shenyang Pharmaceutical University, Shenyang, 110016, China; Key Laboratory of Structure-Based Drug Design and Discovery of Ministry of Education, Shenyang Pharmaceutical University, Shenyang, 110016, China.
Department of Pharmacology, School of Life Sciences and Biopharmaceutics, Shenyang Pharmaceutical University, Shenyang, 110016, China.
出版信息
Eur J Med Chem. 2021 Nov 15;224:113697. doi: 10.1016/j.ejmech.2021.113697. Epub 2021 Jul 10.
β-Agonists that bind to plasmalemmal β-adrenoceptors causing cAMP accumulation are widely used as bronchodilators in chronic respiratory diseases. Here, we designed and synthesized a group of 8-hydroxyquinolin-2(1H)-one analogues and studied their β-agonistic activities with a cellular cAMP assay. Compounds B05 and C08 were identified as potent (EC < 20 pM) and selective β-agonists among the compounds tested. They behaved as partial β-agonists in non-overexpressed HEK293 cells, and possessed rapid smooth muscle relaxant actions and long duration of action in isolated guinea pig tracheal strip preparations. In summary, B05 and C08 are β-agonists with potential applicability in chronic respiratory diseases.
β-激动剂与质膜β-肾上腺素受体结合，导致 cAMP 积累，被广泛用作慢性呼吸道疾病的支气管扩张剂。在这里，我们设计并合成了一组 8-羟基喹啉-2(1H)-酮类似物，并通过细胞 cAMP 测定研究了它们的β激动活性。在测试的化合物中，化合物 B05 和 C08 被鉴定为具有强效（EC < 20 pM）和选择性的β激动剂。它们在未过度表达的 HEK293 细胞中表现为部分β激动剂，并且在分离的豚鼠气管条制剂中具有快速的平滑肌松弛作用和长时间的作用。总之，B05 和 C08 是具有潜在应用于慢性呼吸道疾病的β激动剂。
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